Abstract
Background aims
Mesenchymal stromal cells (MSC) isolated from bone marrow (BM), adipose tissue and umbilical cord blood can be induced to differentiate into hepatocyte-like cells. MSC can also be isolated from umbilical cord Wharton's jelly (UC MSC), which can be easily obtained. UC MSC are more primitive MSC than those isolated from other tissue sources and do not express the major histocompatibility complex (MHC) class II (HLA-DR) antigens. Previous studies have shown that UC MSC are still viable and not rejected 4 months after transplantation as xenografts, without the need for immune suppression, suggesting that they are a favorable cell source for transplantation.
Methods
UC MSC were induced to differentiate into hepatocyte-like cells by a simple one-step protocol with hepatotic growth factor (HGF) and fibroblast growth factor-4 (FGF-4). Differentiated cells were examined for the expression of hepatocyte-specific markers and hepatocyte functions.
Results
UC MSC were isolated. Flow cytometry analysis showed that they expressed the MSC-specific markers. They differentiated into osteoblast-, adipocyte- and chondrocyte-like cells, showing their multipotent differentiation potential. Immunocytochemistry, real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot analysis demonstrated that UC MSC expressed the hepatocyte-specific markers albumin (ALB), human α-fetoprotein (AFP) and cytokeratin 18 (CK-18) following hepatocyte induction. Periodic acid–Schiff staining showed that differentiated UC MSC could store glycogen, and an low-density lipoprotein (LDL)-uptake assay showed that they could uptake LDL.
Conclusions
This study demonstrates that UC MSC can differentiate into functional hepatocyte-like cells following the induction of HGF and FGF-4. UC MSC can serve as a favorable cell source for tissue engineering in the treatment of liver disease.
Acknowledgements
This work was supported by the National Natural Science Foundation of China grant number 30870650 (Xing Wei). The authors wish to acknowledge the financial support of the Li Ka Shing Foundation for this study. The first two authors contributed equally to this work.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.